Dimethylamine, hydrochloride → HCID 69287820, compound

HRID 1766839Notes

Reaction equation

HRID 1766839 reaction equation
[N+:1]([C:4]1[CH:5]=[C:6]([CH:10]=[C:11]([C:13]([F:16])([F:15])[F:14])[CH:12]=1)[C:7]([OH:9])=O)([O-])=O.Cl.[CH3:18][NH:19][CH3:20].C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[Li].[CH2:55]([O:62][C:63]([NH:65][CH2:66][C@H:67]([NH:73][C:74](=[O:79])[CH2:75][C:76]([OH:78])=O)[C@@H:68]([OH:72])[C:69]#[C:70][CH3:71])=[O:64])[C:56]1[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=1>C(Cl)Cl.CN(C=O)C>[CH2:55]([O:62][C:63](=[O:64])[NH:65][CH2:66][C@H:67]([NH:73][C:74](=[O:79])[CH2:75][C:76](=[O:78])[NH:1][C:4]1[CH:12]=[C:11]([C:13]([F:16])([F:15])[F:14])[CH:10]=[C:6]([C:7](=[O:9])[N:19]([CH3:20])[CH3:18])[CH:5]=1)[C@@H:68]([OH:72])[C:69]#[C:70][CH3:71])[C:56]1[CH:57]=[CH:58][CH:59]=[CH:60][CH:61]=1

Participants

8

Reactant 6

HCID 10473Dimethylamine, hydrochlorideHCID 81531Diisopropylethylamine2×HCID 6166023-Nitro-5-(trifluoromethyl)benzoic acidHCID 3028194LithiumHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)2×HCID 69287489HCID 69287489, compound

Product 1

HCID 69287820HCID 69287820, compoundYield 82.7%

Reagents, catalysts & solvents 1

HCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

The compound 3-nitro-5-trifluoromethylbenzoic acid (500 mg, 2.1 mmol) was dissolved in 20 mL of 1:1 CH2Cl2/DMF. The resultant solution was charged sequentially with dimethylamine hydrochloride (174 mg, 2.1 mmol), N,N-diisopropylethylamine (3.7 mL, 21 mmol) and HATU (970 mg, 2.6 mmol). The mixture was stirred for 12 h at RT, concentrated in vacuo, and partitioned between EtOAc and sat. NH4Cl. The aqueous phase was extracted with EtOAc (1×). The combined organic extracts were washed with sat. NaHCO3 and brine, dried (Na2SO4), filtered, and concentrated in vacuo. A portion (107 mg) of this product was dissolved in MeOH (6 mL). This solution was charged with 5% Pd/C, Degussa style (21 mg), stirred under H2 (1 atm) for 12 h at RT, filtered, and concentrated in vacuo. The residue was dissolved in 6 mL of 1:1 CH2Cl2/DMF. The resultant solution was charged sequentially with the lithium salt of N-[(1S,2S)-1-(benzyloxycarbonylamino-methyl)-2-hydroxy-pent-3-ynyl]-malonamic acid (141 mg, 0.4 mmol, see procedure 21a), N, N-diisopropylethylamine (0.35 mL, 2.0 mmol) and HATU (182 mg, 0.5 mmol). The mixture was stirred for 12 h at RT, concentrated in vacuo, and partitioned between EtOAc and sat. NH4Cl. The aqueous phase was extracted with EtOAc (1×). The combined organic extracts were washed with sat. NaHCO3 and brine, dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by flash chromatography to afford {(2S,3S)-2-[2-(3-dimethylcarbamoyl-5-trifluoromethyl-phenylcarbamoyl)-acetylamino]-3-hydroxy-hex-4-ynyl}-carbamic acid benzyl ester as a colorless oil (186 mg, 81% yield). MS found: (M+Na)+=585.3.

Workup

  1. concentrationconcentrated in vacuo
  2. custompartitioned between EtOAc and sat. NH4Cl
  3. extractionThe aqueous phase was extracted with EtOAc (1×)
  4. washThe combined organic extracts were washed with sat. NaHCO3 and brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. dissolutionA portion (107 mg) of this product was dissolved in MeOH (6 mL)
  9. additionThis solution was charged with 5% Pd/C, Degussa style (21 mg)
  10. stirringstirred under H2 (1 atm) for 12 h at RT
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. dissolutionThe residue was dissolved in 6 mL of 1:1 CH2Cl2/DMF
  14. stirringThe mixture was stirred for 12 h at RT
  15. concentrationconcentrated in vacuo
  16. custompartitioned between EtOAc and sat. NH4Cl
  17. extractionThe aqueous phase was extracted with EtOAc (1×)
  18. washThe combined organic extracts were washed with sat. NaHCO3 and brine
  19. dry with materialdried (Na2SO4)
  20. filtrationfiltered
  21. concentrationconcentrated in vacuo
  22. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-9d5c3711f48e43d9bfae3025c67d97a6
Source dataset
uspto-grants-2007_06
Patent number
US07230133B2

Reaction notes

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